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WHAT DO WE ALREADY KNOW?

Most breast cancer appears to be caused by a combination of inherited (genetic) and environmental exposure factors. The already identified inherited genes (BRCA 1 and 2) account for only perhaps 5% of breast cancer cases. The identified environmental exposures –“risk factors” –obesity, excess alcohol, late age at first full term pregnancy, limited exercise—are not easily changed, and also do not explain the majority of breast cancer cases. Think—how many times have you heard someone say they were so surprised about getting breast cancer because they had no family history of this disease and they exercised and ate right. Exactly. SO:

THE BIG ISSUES

#1. THE GENETIC BASIS OF BREAST CANCER IS UNKNOWN IN THE MAJORITY OF WOMEN WHO DEVELOP THIS DISEASE. WE NEED TO FIND THE OTHER CRITICAL GENES WHICH CAUSE THIS CANCER.

#2. IT IS VERY LIKELY THAT THERE ARE OTHER CHANGEABLE ENVIRONMENTAL EXPOSURES WHICH ARE IMPORTANT IN BREAST CANCER DEVELOPMENT.


Causation study 1: Consanguinity and recessive genes in breast cancer.
Generously funded by a grant from the Canadian Breast Cancer Research Alliance

Children whose parents are first cousins have an increased risk for “recessive” genetic diseases, such as cystic fibrosis; but little is known about the risk of breast cancer in similar families.

Populations where first-cousin marriages are common (especially South Asia and the Middle East) are therefore ideal to search for new breast cancer-susceptibility genes. In Bangladesh 20% of women now in their 30s and 40s have parents who are first cousins. In this study we will use a novel analytic technique to compare genetic factors between 400 Bangladeshi breast cancer patients and their 400 cancer-free sisters. We began recruitment of these women in the fall of 2010.

To our knowledge ours is the only study designed specifically to establish whether consanguinity is a risk factor for breast cancer and which seeks to localize likely responsible genes.

We will use a novel analytic method which combines linkage and association approaches in homozygosity mapping. Rather than studying multiple individuals in the same family (e.g. "traditional linkage analysis"), we will use homozygosity mapping to study affected individuals (breast cancer patients) of consanguinous parentage from different families. The comparison between breast cancer cases from consanguinous parents and their unaffected sisters is also novel.

To our knowledge, the Runs of Homozygosity (ROH) algorithm has not yet been used in breast (or other) cancer research.

Why is this research important?

If we can find recessive genes that are important in breast cancer in this efficient study, we can be on the road to explaining ‘surprise” breast cancers that occur throughout the world.

Our Research Team

Ophira Ginsburg M.D.
Assistant Professor, Medical Oncology
Adjunct Scientist, Women's College Hospital, University of Toronto, Toronto, Canada
Madison, Wisconsin
Mohammad R. Akbari
Women's College Research Institute
University of Toronto
Toronto, Canada
Dr. Rahela Munim Dipi, MBBS, FCPS, M.D.
Assistant Professor, Radiology & Imaging
Bangabandhu Sheikh Mujib Medical University (BSMMU)
Dhaka, Bangladesh
Dr. Syed Mozammel Hossain
Associate Professor of Obstetrics and Gynecology
Khulna Medical College
Khulna, Bangladesh
Dr. Steven Narod
Professor, Dalla Lana School of Public Health
Women's College Research Institute
Toronto, Canada
Mohammad Golam Mostafa
Pathology Investigator
Professor of Histopathology, National Institute of Cancer Research and Hospital, Mohakhali, Dhaka, Bangladesh

To learn more: Write to Dr. Ophira Ginsburg at ophira.ginsburg@utoronto.ca

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Causation study 2: Inherited genes and environmental causes of breast cancer in a low risk population of women in Vietnam

There may be unique genes (in the BRCA1 and 2 families) conferring inherited risk of breast cancer among women in usually “low risk” countries in Asia (countries where the likelihood of breast cancer developing is much less-- perhaps one quarter of that-- among American women for example). These genes might be most likely among young women in these countries who develop breast cancer. If such genes could be identified, this would be important for identifying women everywhere with inherited risks for breast cancer and explain some fraction of the causes of breast cancer in Asian women.

In this study in Vietnam, 500 young women (under age 50) with breast cancer and 500 similarly aged women there without breast cancer are having DNA from their blood analyzed for the full spectrum of possible BRCA1 and 2 mutations. Additionally all women are answering a detailed questionnaire about possible environmental causes of breast cancer. As of summer 2010, 300 pairs of women have been analyzed for genetic mutations and three mutations have been found.

 
  Dr. Richard Love, center with research team

 

Dr. Ophira Ginsburg in genetic counseling
   
  Intake with Dr. Nguyen Dieu Linh  

Why is this research important?

Most studies of breast cancer are in women of northern European/American genetic and environmental backgrounds, where breast cancer is much more frequent than in Asia. It is however in our differences—genetically and environmentally-that we can get important indicators for what causes disease like breast cancer.

Our Research Team

Ophira Ginsburg M.D.
Assistant Professor, Medical Oncology
Adjunct Scientist, Women's College Hospital, University of Toronto, Toronto, Canada
Madison, Wisconsin
Dr. Steven Narod
Professor, Dalla Lana School of Public Health
Women's College Research Institute
Toronto, Canada
Dr. Nguyen Dinh Tung, M.D., Ph.D.
Principle Investigator
Hue Central Hospital
Hue, Vietnam
Dr. Ta Van To, M.D., Ph.D.
Professor of Pathology
Hospital K
Head of Cytopathology Department
National Cancer Institute
Hanoi, Vietnam
Dr. Njuyen Van Dinh, Chief
Department of Breast Surgery
National Cancer Institute
Hospital K
Hanoi, Vietnam
Dr. Nguyen Dieu Linh
Clinical Investigator
Hospital K
Hanoi, Vietnam
Dr. Le Hong Quang
Clinical Investigator
Hospital K
Hanoi, Vietnam
Dr. Tran Tu Quy
Principle Investigator
Danang General Hospital
Danang, Vietnam

To learn more: Write to Dr. Ophira Ginsburg at ophira.ginsburg@utoronto.ca

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Causation study 3: Environmental causes of breast cancer in Philipino and Vietnamese young women with breast cancer.

The rates of developing breast cancer among Philipino and Vietnamese women are about one quarter to one half of the rates among American women. Major differences in “lifestyle” –what women eat and are exposed to in their daily lives may account for these differences in rates. The majority of breast cancers have hormonal receptors (estrogen and progesterone receptors) in the tumors.

In this study all of the 740 women participating in the IBCRF “Randomized clinical trial of adjuvant luteal phase oophorectomy and tamoxifen in pre-menopausal women with operable breast cancer (link) and for each of these women two similarly aged women without breast cancer are providing detailed information about possibly important exposures. Unusual lifestyles (working at night for example), and nutritional exposures are of particular interest. The researchers will also correlate certain exposures with characteristics of the tumors in the women with cancers.

Why is this research important?

Most studies of breast cancer are in women of northern European/American genetic and environmental backgrounds, where breast cancer is much more frequent than in Asia. It is however in our differences—genetically and environmentally-that we can get important indicators for what causes disease like breast cancer.

Our Research Team

Amy Dietz
Associate Professor
Department of Population Health Sciences
University of Wisconsin – Madison, Wisconsin
Dr. Adriano V. Laudico
Principal Investigator Professor Emeritus of Surgery
University of the Philippines, Manila
Dr. Maria Rica Mirasol-Lumague
Principal Investigator
Rizal Medical Center
Manila, Philippines
Dr. Narciso Navarro, Jr.
Principle Investigator
Santo Tomas University
Manila, Philippines
Dr. Jonathan S. Salvador
Principal Investigator
East Avenue Medical Center
Manila, Philippines
Dr. Gemma B. Uy
Co-Investigator Clinical Associate Professor of Surgery
University of the Philippines, Manila
Dr. Arturo S.
de La Peña
Co-Investigator Professor of Surgery
University of the Philippines,
Manila
Dr. Rodney B. Dofitas
Co-Investigator Professor of Surgery
University of the Philippines,
Manila
Ms. Victoria Medina
Epidemiologist
College of Public Health,
University of the Philippines, Manila
Dr. Njuyen Van Dinh, Chief
Department of Breast Surgery
National Cancer Institute
Hospital K
Hanoi, Vietnam
Dr. Le Hong Quang
Clinical Investigator
Hospital K
Hanoi, Vietnam


To learn more: Write to Dr Amy Trentham-Dietz at trentham@wisc.edu


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